Calmodulin, a ubiquitous calcium-binding protein recognizes changes in intracellular calcium concentration induced by external stimuli and transmits this information to cellular control are cAMP phosphodiesterase, protein kinases and a protein phosphatase (calcineurin) which confer upon calmodulin the ability to effect a phosphatase (calcineurin) which confer upon calmodulin the ability to effect a tight couplin between cAMP and calcium. Our major goal is to understand the mechanism of regulation of cellular processes by calmodulin. Previous work showed that binding of calcium to calmodulin is an order process that generate at least three different calmodulin conformers. Studies with calmodulin fragments and with a covalent adduct of calmodulin and and phenothiazine (CAPP Calmodulin) demonstrated that interaction of calmodulin with its several targets requires the integrity of different portions of the calmodulin molecule. Anticalmodulin drugs, such as phenothiazines, interact with either one of two sites located between residues 31 and 74 and 148. Calmodulin also contains two protein-binding sites located on each half of the molecule. Some enzymes need to interact at both sites to be activated. Others require only the one located in the COOH-terminal. With yet a third class of enzymes either one of the two can substitute for the native protein.